Penetration of Colistin into Cerebrospinal Fluid

ABSTRACT Colistin is used to treat infections caused by multidrug-resistant gram-negative bacteria (MDR-GNB). It is administered intravenously in the form of colistin methanesulfonate (CMS), which is hydrolyzed in vivo to the active drug. However, pharmacokinetic data are limited. The aim of the present study was to characterize the pharmacokinetics of CMS and colistin in a population of critically ill patients. Patients receiving colistin for the treatment of infections caused by MDR-GNB were enrolled in the study; however, patients receiving a renal replacement therapy were excluded. CMS was administered at a dose of 3 million units (240 mg) every 8 h. Venous blood was collected immediately before and at multiple occasions after the first and the fourth infusions. Plasma CMS and colistin concentrations were determined by a novel liquid chromatography-tandem mass spectrometry method after a rapid precipitation step that avoids the significant degradation of CMS and colistin. Population pharmacokinetic analysis was performed with the NONMEM program. Eighteen patients (6 females; mean age, 63.6 years; mean creatinine clearance, 82.3 ml/min) were included in the study. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.046 h and 2.3 h, respectively. The clearance of CMS was 13.7 liters/h. For colistin, a one-compartment model was sufficient to describe the data, and the estimated half-life was 14.4 h. The predicted maximum concentrations of drug in plasma were 0.60 mg/liter and 2.3 mg/liter for the first dose and at steady state, respectively. Colistin displayed a half-life that was significantly long in relation to the dosing interval. The implications of these findings are that the plasma colistin concentrations are insufficient before steady state and raise the question of whether the administration of a loading dose would benefit critically ill patients.

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Factitious Meningitis: A Recurring Problem

Infection Control and Hospital Epidemiology ◽

10.1086/645760 ◽

1988 ◽

Vol 9 (11) ◽

pp. 501-503 ◽

Cited By ~ 2

Author(s):

Robert L. Penn ◽

Richard Normand ◽

Stephen A. Klotz

Keyword(s):

Cerebrospinal Fluid ◽

Lumbar Puncture ◽

Retrospective Review ◽

False Positive ◽

Commercial Products ◽

Gram Negative ◽

Specimen Tube

AbstractAlthough gram-negative meningitis is rare in our hospital, between July, 1982 and July, 1983 clusters of cerebrospinal fluid (CSF) smears were reported positive for gram-negative bacilli. Fourteen specimens were obtained by diagnostic lumbar punctures, and one was obtained during a myelogram. No CSF cultures were positive, and a diagnosis of factitious meningitis was eventually established for each patient. Nonviable gram-negative bacilli were found in 6.7% of manometers, and 23.3% to 90% of the specimen tubes tested from the same lots of commercial lumbar puncture trays. It was estimated that there were between 44 and 333 organisms per specimen tube. Two lots of the commercial myelogram trays yielded nonviable gram-negative bacilli from 50% of the specimen tubes and 33.3% of the manometers tested. Retrospective review of laboratory records for 1982 and 1983 revealed 23 total CSF smears positive for gram-negative bacilli. No CSF grew gram-negative bacilli, and chart reviews confirmed a diagnosis of factitious meningitis in each case. In addition to the clusters of false-positive smears, this had occurred sporadically in both years. The problem did not recur after separate sterile tubes were provided for CSF collection. Physicians and laboratories should be aware that nonviable contaminants in commercial products may be a source of false-positive CSF gram-stained smears.

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Colistin Population Pharmacokinetics after Application of a Loading Dose of 9 MU Colistin Methanesulfonate in Critically Ill Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00554-15 ◽

2015 ◽

Vol 59 (12) ◽

pp. 7240-7248 ◽

Cited By ~ 61

Author(s):

Ilias Karaiskos ◽

Lena E. Friberg ◽

Konstantinos Pontikis ◽

Konstantinos Ioannidis ◽

Vasiliki Tsagkari ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Compartment Model ◽

Population Pharmacokinetic Analysis ◽

Pharmacokinetic Analysis ◽

Population Pharmacokinetic ◽

Loading Dose ◽

Gram Negative ◽

Link Type ◽

Colistin Methanesulfonate

ABSTRACTColistin has been revived, in the era of extensively drug-resistant (XDR) Gram-negative infections, as the last-resort treatment in critically ill patients. Recent studies focusing on the optimal dosing strategy of colistin have demonstrated the necessity of a loading dose at treatment initiation (D. Plachouras, M. Karvanen, L. E. Friberg, E. Papadomichelakis, A. Antoniadou, I. Tsangaris, I. Karaiskos, G. Poulakou, F. Kontopidou, A. Armaganidis, O. Cars, and H. Giamarellou, Antimicrob Agents Chemother 53:3430–3436, 2009,http://dx.doi.org/10.1128/AAC.01361-08; A. F. Mohamed, I. Karaiskos, D. Plachouras, M. Karvanen, K. Pontikis, B. Jansson, E. Papadomichelakis, A. Antoniadou, H. Giamarellou, A. Armaganidis, O. Cars, and L. E. Friberg, Antimicrob Agents Chemother 56:4241– 4249, 2012,http://dx.doi.org/10.1128/AAC.06426-11; S. M. Garonzik, J. Li, V. Thamlikitkul, D. L. Paterson, S. Shoham, J. Jacob, F. P. Silveira, A. Forrest, and R. L. Nation, Antimicrob Agents Chemother 55:3284–3294, 2011,http://dx.doi.org/10.1128/AAC.01733-10). In 19 critically ill patients with suspected or microbiologically documented infections caused by XDR Gram-negative strains, a loading dose of 9 MU colistin methanesulfonate (CMS) (∼270 mg colistin base activity) was administered with a maintenance dose of 4.5 MU every 12 h, commenced after 24 h. Patients on renal replacement were excluded. CMS infusion was given over 30 min or 1 h. Repeated blood sampling was performed after the loading dose and after the 5th or 6th dose. Colistin concentrations and measured CMS, determined after hydrolization to colistin and including the partially sulfomethylated derivatives, were determined with a liquid chromatography-tandem mass spectrometry assay. Population pharmacokinetic analysis was conducted in NONMEM with the new data combined with data from previous studies. Measured colistimethate concentrations were described by 4 compartments for distribution and removal of sulfomethyl groups, while colistin disposition followed a 1-compartment model. The average observed maximum colistin A plus B concentration was 2.65 mg/liter after the loading dose (maximum time was 8 h). A significantly higher availability of the measured A and B forms of colistimethate and colistin explained the higher-than-expected concentrations in the present study compared to those in previous studies. Creatinine clearance was a time-varying covariate of colistimethate clearance. The incidence of acute renal injury was 20%.

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Diagnostic yield of cerebrospinal fluid analysis in status epilepticus: an 8-year cohort study

Journal of Neurology ◽

10.1007/s00415-021-10447-3 ◽

2021 ◽

Author(s):

Tolga D. Dittrich ◽

Sira M. Baumann ◽

Saskia Semmlack ◽

Gian Marco De Marchis ◽

Sabina Hunziker ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Status Epilepticus ◽

Lumbar Puncture ◽

Diagnostic Yield ◽

Autoimmune Encephalitis ◽

Infectious Complications ◽

Adult Patients ◽

University Hospital ◽

Fluid Analysis ◽

Neurologic Function

Abstract Background We investigate the frequency and diagnostic yield of cerebrospinal fluid (CSF) analysis in adult patients with status epilepticus (SE) and its impact on the outcome. Methods From 2011 to 2018, adult patients treated at the University Hospital Basel were included. Primary outcomes were defined as the frequency of lumbar puncture and results from chemical, cellular, and microbiologic CSF analyses. Secondary outcomes were differences between patients receiving and not receiving lumbar puncture in the context of SE. Results In 18% of 408 patients, a lumbar puncture was performed. Of those, infectious pathogens were identified in 21% with 15% detected ± 24 h around SE diagnosis. 74% of CSF analyses revealed abnormal chemical or cellular components without infectious pathogens. Screening for autoimmune diseases was only performed in 22%. In 8%, no or late (i.e., > 24 after SE diagnosis) lumbar puncture was performed despite persistent unknown SE etiology in all, transformation into refractory SE in 78%, and no recovery to premorbid neurologic function in 66%. Withholding lumbar puncture was associated with no return to premorbid neurologic function during hospital stay independent of potential confounders. Not receiving a lumbar puncture was associated with presumed known etiology and signs of systemic infectious complications. Conclusions Withholding lumbar puncture in SE patients is associated with increased odds for no return to premorbid neurologic function, and CSF analyses in SE detect infectious pathogens frequently. These results and pathologic chemical and cellular CSF findings in the absence of infections call for rigorous screening to confirm or exclude infectious or autoimmune encephalitis in this context which should not be withheld.

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Combined Intravenous and Intraventricular Administration of Colistin Methanesulfonate in Critically Ill Patients with Central Nervous System Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01461-12 ◽

2013 ◽

Vol 57 (4) ◽

pp. 1938-1940 ◽

Cited By ~ 41

Author(s):

Mairi Ziaka ◽

Sophia L. Markantonis ◽

Marizoza Fousteri ◽

Paris Zygoulis ◽

Dimitris Panidis ◽

...

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Critically Ill ◽

Intravenous Administration ◽

Critically Ill Patients ◽

External Ventricular Drain ◽

Central Nervous System Infection ◽

Intraventricular Administration ◽

Colistin Methanesulfonate

ABSTRACTColistin pharmacokinetics were prospectively studied after intravenous administration of colistin methanesulphonate in critically ill patients without central nervous system infection (controls,n= 5) and in patients with external ventricular drain-associated ventriculitis after intravenous administration (EVDViv,n= 3) or combined intravenous/intraventricular administration (EVDVcomb,n= 4). Cerebrospinal fluid (CSF)/serum colistin concentration ratios were higher in EVDViv than in control patients (11% versus 7%,P≤ 0.05) and in EVDVcomb compared to all other patients (P< 0.0001). CSF colistin concentrations above the MIC of 0.5 μg/ml were achieved only in EVDVcomb patients.

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Factitious Meningitis: A Recurring Problem

Infection Control and Hospital Epidemiology ◽

10.2307/30146546 ◽

1988 ◽

Vol 9 (11) ◽

pp. 501-503 ◽

Cited By ~ 1

Author(s):

Robert L. Penn ◽

Richard Normand ◽

Stephen A. Klotz

Keyword(s):

Cerebrospinal Fluid ◽

Lumbar Puncture ◽

Retrospective Review ◽

False Positive ◽

Commercial Products ◽

Gram Negative ◽

Specimen Tube

AbstractAlthough gram-negative meningitis is rare in our hospital, between July, 1982 and July, 1983 clusters of cerebrospinal fluid (CSF) smears were reported positive for gram-negative bacilli. Fourteen specimens were obtained by diagnostic lumbar punctures, and one was obtained during a myelogram. No CSF cultures were positive, and a diagnosis of factitious meningitis was eventually established for each patient. Nonviable gram-negative bacilli were found in 6.7% of manometers, and 23.3% to 90% of the specimen tubes tested from the same lots of commercial lumbar puncture trays. It was estimated that there were between 44 and 333 organisms per specimen tube. Two lots of the commercial myelogram trays yielded nonviable gram-negative bacilli from 50% of the specimen tubes and 33.3% of the manometers tested. Retrospective review of laboratory records for 1982 and 1983 revealed 23 total CSF smears positive for gram-negative bacilli. No CSF grew gram-negative bacilli, and chart reviews confirmed a diagnosis of factitious meningitis in each case. In addition to the clusters of false-positive smears, this had occurred sporadically in both years. The problem did not recur after separate sterile tubes were provided for CSF collection. Physicians and laboratories should be aware that nonviable contaminants in commercial products may be a source of false-positive CSF gram-stained smears.

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Effectiveness of Cefotaxime in Gram-negative Meningitis

Neurosurgery ◽

10.1227/00006123-198411000-00007 ◽

1984 ◽

Vol 15 (5) ◽

pp. 679-682 ◽

Cited By ~ 5

Author(s):

Jack L. LeFrock ◽

Abdolghader Molavi ◽

Bruce Smith ◽

Perry Black ◽

Manuel Rosenberg ◽

...

Keyword(s):

Escherichia Coli ◽

Cerebrospinal Fluid ◽

Klebsiella Pneumoniae ◽

Haemophilus Influenzae ◽

Serratia Marcescens ◽

Adult Patients ◽

Neurosurgical Procedure ◽

Gram Negative ◽

The Mean

Abstract We treated 12 adult patients who had gram-negative bacillary meningitis with cefotaxime administered intravenously at a dose of 2 g every 4 hours. The etiological organisms included Haemophilus influenzae (3 cases), Serratia marcescens (3 cases), Klebsiella pneumoniae (3 cases), Escherichia coli (2 cases), and Enterobacter (1 case). The infection followed a neurosurgical procedure in 6 cases. The mean inhibitory and bactericidal concentrations of cefotaxime for the isolates ranged from 0.125 to 0.25 ug/ml. The cerebrospinal fluid (CSF) concentrations of cefotaxime ranged from 5.0 to 15.2 ug/ml, and the CSF bactericidal titers were 1:64 to 1:128. The CSF in all patients was sterilized within 96 hours. All 12 patients recovered, and there were no relapses.

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An unusual Case of Meningitis

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2015/262479 ◽

2015 ◽

Vol 26 (3) ◽

pp. e62-e64 ◽

Cited By ~ 5

Author(s):

Eric DR Pond ◽

Sameh El-Bailey ◽

Duncan Webster

Keyword(s):

Cerebrospinal Fluid ◽

Bacterial Meningitis ◽

Lumbar Puncture ◽

Pasteurella Multocida ◽

Unusual Case ◽

Definitive Treatment ◽

Gram Negative ◽

Level Of Consciousness ◽

Low Glucose ◽

Animal Exposure

Pasteurella multocidais a rare cause of bacterial meningitis. A 56-year-old man with several pets developed a profoundly decreased level of consciousness following left tympanomastoidectomy. Lumbar puncture produced cerebrospinal fluid with the typical findings of meningitis (low glucose, high protein, high leukocytes). Cultures from the cerebrospinal fluid and a swab of the left ear revealed Gram-negative coccobacillus identified asP multocida. The organism was sensitive to ceftriaxone, ampicillin and penicillin, and a 14-day course of intravenous penicillin was used as definitive treatment, resulting in full recovery. Although rare,P multocidashould be considered as a potential cause of meningitis in patients with animal exposure, particularly in the setting of recent cranial surgery.

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